Impact of glucagon response on postprandial hyperglycemia in men with impaired glucose tolerance and type 2 diabetes mellitus

Henkel, Elena; Menschikowski, Mario; Koehler, Carsta; Leonhardt, W.; Hanefeld, Markolf

doi:10.1016/j.metabol.2005.03.024

Cited by 65 publications

(58 citation statements)

References 29 publications

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“…In the fasting state, adipose tissue is the most important contributor (ϳ80%) to the plasma NEFA concentrations, and it is well known that subcutaneous adipocytes have high lipolytic activity (24,25). We hypothesized that a glucagon-mediated lipolytic effect on peripheral adipose tissue may occur in the fasting state when patients are fed a CHO-rich diet, relocating fatty acids from peripheral to central body fat depots (26,27). Alternatively, it is possible that hepatic lipogenesis may have contributed to the postprandial increase in plasma concentrations of glucose and insulin observed in individuals fed CHO-rich diets that may stimulate de novo lipogenesis (28,29).…”

Section: Effects Of Macronutrient Diet Composition On Energy Balancementioning

confidence: 99%

Monounsaturated Fat–Rich Diet Prevents Central Body Fat Distribution and Decreases Postprandial Adiponectin Expression Induced by a Carbohydrate-Rich Diet in Insulin-Resistant Subjects

et al. 2007

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OBJECTIVE -Central obesity is associated with insulin resistance through factors that are not fully understood. We studied the effects of three different isocaloric diets on body fat distribution, insulin sensitivity, and peripheral adiponectin gene expression. RESEARCH DESIGN AND METHODS-Eleven volunteers, offspring of obese type 2 diabetic patients with abdominal fat deposition, were studied. These subjects were considered insulin resistant as indicated by Matsuda index values Ͻ4 after an oral glucose tolerance test, and they maintained A1C Ͻ6.5% without therapeutic intervention. All subjects underwent three dietary periods of 28 days each in a crossover design: 1) diet enriched in saturated fat (SAT), 2) diet rich in monounsaturated fat (MUFA) (Mediterranean diet), and 3) diet rich in carbohydrates (CHOs).RESULTS -Weight, body composition, and resting energy expenditure remained unchanged during the three sequential dietary periods. Using dual-energy X-ray absorptiometry we observed that when patients were fed a CHO-enriched diet, their fat mass was redistributed toward the abdominal depot, whereas periphery fat accumulation decreased compared with isocaloric MUFA-rich and high-SAT diets (ANOVA P Ͻ 0.05). Changes in fat deposition were associated with decreased postprandial mRNA adiponectin levels in peripheral adipose tissue and lower insulin sensitivity index values from a frequently sampled insulin-assisted intravenous glucose tolerance test in patients fed a CHO-rich diet compared with a MUFA-rich diet (ANOVA P Ͻ 0.05).CONCLUSIONS -An isocaloric MUFA-rich diet prevents central fat redistribution and the postprandial decrease in peripheral adiponectin gene expression and insulin resistance induced by a CHO-rich diet in insulin-resistant subjects. Diabetes Care 30:1717-1723, 2007A positive energy balance, which leads to obesity, is associated with insulin resistance and an increased risk of type 2 diabetes. According to our studies in rodents, adipose tissue expandability seems to be a key determinant linking obesity and its associated complications (1,2). Expansion of the intra-abdominal depot has been associated with increased insulin resistance, as well as with an increased incidence of fatty liver and ␤-cell failure (3,4).The factors that regulate body fat distribution are not well understood. We hypothesize that the specific macronutrient composition of the diet may be an important environmental factor that controls nutrient partitioning to specific adipose tissue depots (5). It is now well established that adipose tissue is not simply an energy storage organ but is, in fact, the "largest" endocrine gland controlling energy homeostasis (6). It is conceivable that specific diet composition may directly influence the molecular events that govern gene expression in adipocytes (7), adipokine production, and adipocyte lipid and glucose metabolism (8).Adiponectin adipocyte-secreted adipokine plays an important role in modulating insulin sensitivity and concentrations of circulating plasma glucose and noneste...

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Section: Effects Of Macronutrient Diet Composition On Energy Balancementioning

confidence: 99%

Monounsaturated Fat–Rich Diet Prevents Central Body Fat Distribution and Decreases Postprandial Adiponectin Expression Induced by a Carbohydrate-Rich Diet in Insulin-Resistant Subjects

et al. 2007

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“…Patients with type 2 diabetes have impairments in the incretin system, and furthermore, they exhibit elevated plasma glucagon levels that are nonsuppressible the first hour after oral glucose administration (23,31). The attenuated and delayed glucagon suppression has only been found after oral ingestion of glucose, while isoglycemic intravenous administration of glucose has resulted in more or less normal suppression of glucagon (22).…”

Section: Discussionmentioning

confidence: 99%

GLP-1 Restores Altered Insulin and Glucagon Secretion in Posttransplantation Diabetes

et al. 2016

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OBJECTIVEDevelopment of posttransplantation diabetes (PTDM) is characterized by reduced insulin secretion and sensitivity. We aimed to investigate whether hyperglucagonemia could play a role in PTDM and to examine the insulinotropic and glucagonostatic effects of the incretin hormone glucagon-like peptide 1 (GLP-1) during fasting and hyperglycemic conditions, respectively. RESEARCH DESIGN AND METHODSRenal transplant recipients with (n = 12) and without (n = 12) PTDM underwent two separate experimental days with 3-h intravenous infusions of GLP-1 (0.8 pmol/kg/min) and saline, respectively. After 1 h of infusion, a 2-h hyperglycemic clamp (fasting plasma glucose + 5 mmol/L) was established. Five grams of arginine was given as an intravenous bolus 10 min before termination of the clamp. RESULTSFasting concentrations of glucagon (P = 0.92) and insulin (P = 0.23) were similar between the groups. In PTDM patients, glucose-induced glucagon suppression was significantly less pronounced (maximal suppression from baseline: 43 6 12 vs. 65 6 12%, P < 0.001), while first-and second-phase insulin secretion were significantly lower. The PTDM group also exhibited a significantly lower insulin response to arginine (P = 0.01) but similar glucagon and proinsulin responses compared with control subjects. In the preclamp phase, GLP-1 lowered fasting plasma glucose to the same extent in both groups but reduced glucagon only in PTDM patients. During hyperglycemic clamp, GLP-1 reduced glucagon concentrations and increased first-and second-phase insulin secretion in both groups. CONCLUSIONSPTDM is characterized by reduced glucose-induced insulin secretion and attenuated glucagon suppression during a hyperglycemic clamp. Similar to the case in type 2 diabetes, GLP-1 infusion seems to improve (insulin) or even normalize (glucagon) these pathophysiological defects.In renal transplant recipients, cardiovascular disease persists as the leading cause of premature death (1). Development of posttransplantation diabetes (PTDM) is associated with further increased cardiovascular risk and mortality (2-4). PTDM is primarily believed to be a variant of type 2 diabetes possibly induced by immunosuppressive therapy (5) and/or viral infections (e.g., cytomegalovirus and hepatitis C) that reduce both insulin secretion and insulin sensitivity (6). Importantly, the risk of PTDM can be significantly reduced by proper dosing of the immunosuppressive

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“…#, p < 0.05 obese diabetic patients vs non-diabetic subjects; ##, p < 0.05 non-obese diabetic patients vs non-diabetic subjects; *, p < 0.05 obese diabetic patients vs non-obese diabetic patients; N.S., not significant total AUC of them, and the ratio had the closer correlation with the former than with the latter. In previous studies, the early postprandial glucagon secretion was correlated with 6-hour AUC of postprandial glucose levels [11], and the 30-minute molar ratio of insulin to glucagon was also correlated with 5-hour AUC of total systemic glucose appearance using an isotope technique [12]. Our more detailed time course analysis confirmed the previous results and further suggested that the early postprandial glucagon surge directly affected the early postprandial hyperglycemia, while the deteriorated early postprandial balance between glucagon and insulin secretion might reflect especially the late postprandial hyperglycemia in diabetic patients.…”

Section: Mixed-meal Tolerance Testmentioning

confidence: 93%

Early postprandial glucagon surge affects postprandial glucose levels in obese and non-obese patients with type 2 diabetes

et al. 2013

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Type 2 diabeTes is characterized by impaired insulin secretion and insulin resistance. In this type of diabetes, insufficient suppression of glucagon secretion after oral glucose or meal ingestion and fasting hyperglucagonemia have been described [1][2][3][4]. However, an association between postprandial glucose and glucagon levels has not been fully elucidated. In previous studies, almost all patients were obese or overweight and hyperinsulinemic. In contrast, Japanese type 2 diabetic patients are often non-obese, and their mean body mass index (BMI) is 23.1, which is lower than that of the Caucasian subjects in the UK Prospective Diabetes Study [5]. Indeed, in Japanese criteria, obesity is diagnosed when the BMI is equal to or higher than 25. In few Japanese previous reports, exaggerated glucagon Early postprandial glucagon surge affects postprandial glucose levels in obese and non-obese patients with type 2 diabetes abstract. Postprandial glucagon secretion was shown to be dysregulated in patients with type 2 diabetes. However, the differences in secretory patterns between obese and non-obese patients and their physiological effects on plasma glucose levels are not fully understood. This study population consisted of 21 (10 obese and 11 non-obese) consecutive patients with type 2 diabetes admitted for glycemic control. A 3-hour mixed-meal tolerance test was performed after glycemic control improved. Six non-diabetic subjects were also enrolled in the test. Postprandial glucagon levels increased after 30 min in diabetic patients but not in non-diabetic subjects. The glucagon levels in obese diabetic patients were significantly higher than those in non-obese diabetic patients, while the percent values of postprandial glucagon levels were not different between these groups. In diabetic patients, there were significant positive correlations between the percent value at 30 min and the early postprandial glucose levels at 0, 15 and 30 min and the areas under the curve (AUC 0-30 and AUC ). Interestingly, the ratio of this percent glucagon value to the C-peptide level at 30 min was significantly associated with the late half of the postprandial glucose levels at 90, 120, 150 and 180 min and the AUC 90-180 . This is the first report that demonstrates the glucagon secretory patterns and the close correlations in detailed time course between the early postprandial glucagon response and the early and the late half of the postprandial glucose levels in obese and non-obese patients with type 2 diabetes.

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Impact of glucagon response on postprandial hyperglycemia in men with impaired glucose tolerance and type 2 diabetes mellitus

Cited by 65 publications

References 29 publications

Monounsaturated Fat–Rich Diet Prevents Central Body Fat Distribution and Decreases Postprandial Adiponectin Expression Induced by a Carbohydrate-Rich Diet in Insulin-Resistant Subjects

Monounsaturated Fat–Rich Diet Prevents Central Body Fat Distribution and Decreases Postprandial Adiponectin Expression Induced by a Carbohydrate-Rich Diet in Insulin-Resistant Subjects

GLP-1 Restores Altered Insulin and Glucagon Secretion in Posttransplantation Diabetes

Early postprandial glucagon surge affects postprandial glucose levels in obese and non-obese patients with type 2 diabetes

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